Identification of a small molecule HIV-1 inhibitor that targets the capsid hexamer

被引：17
|
作者：
Xu, Jimmy P. [1 ]
Branson, Jeffrey D. [1 ]
Lawrence, Rae [2 ]
Cocklin, Simon [1 ]
机构：
[1] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Rooms 10302-10306,245 North 15th St, Philadelphia, PA 19102 USA
[2] Cresset, New Cambridge House,Bassingbourn Rd, Litlington SG8 0SS, Cambs, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 03期
关键词：
Computer-aided drug design; Field-based virtual screening; HIV-1 capsid protein; Antiviral; Surface plasmon resonance; N-TERMINAL DOMAIN; ACTIVITY-RELATIONSHIPS SAR; CRYSTAL-STRUCTURES; HUMAN CYCLOPHILIN; BINDING-SITE; CA PROTEIN; OPTIMIZATION; REPLICATION; DISCOVERY; DIMERIZATION;
D O I：
10.1016/j.bmcl.2015.12.087
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The HIV-1 CA protein is an attractive therapeutic target for the development of new antivirals. An inter-protomer pocket within the hexamer configuration of the CA, which is a binding site for key host dependency factors, is an especially appealing region for small molecule targeting. Using a field-based pharmacophore derived from an inhibitor known to interact with this region, coupled to biochemical and biological assessment, we have identified a new compound that inhibits HIV-1 infection and that targets the assembled CA hexamer. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：824 / 828
页数：5
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